A Phase 1/2 Study to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies

• ClinicalTrials.gov Identifier: NCT02963831
• Recruitment Status: Active, not recruiting
• First Posted: November 15, 2016
• Last Update Posted: November 16, 2021
• Sponsor: Ludwig Institute for Cancer Research
• Collaborators: Cancer Research Institute, New York City; MedImmune LLC; Targovax ASA
• Information provided by (Responsible Party): Ludwig Institute for Cancer Research

Study Description

Brief Summary:

This is a two-part Phase 1/2 dose escalation and dose expansion study of the GMCSF-encoding adenovirus, ONCOS-102, in combination with anti-programmed death ligand-1 (PDL1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed platinum-resistant or refractory epithelial ovarian cancer or colorectal cancer.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer; Platinum-resistant Ovarian Cancer; Appendiceal Cancer	Biological: ONCOS-102; Drug: Durvalumab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Dose Escalation Study With Expansion Cohorts to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
• Actual Study Start Date: September 7, 2017
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation; During Phase 1 of the study, subjects will be evaluated for DLTs before proceeding to a subsequent cohort. Dose escalation for the determination of RCD will be performed based on the available dose levels and the respective rules for a standard 3 + 3 dose escalation study design. For Cohort A, ONCOS-102 will be given as monotherapy the first six weeks, and then durvalumab (1500 mg) will be starting on day 71. For Cohorts B and C, ONCOS-102 will be administered for a total of 6 weeks while durvalumab will be given for a total of 12 four-week cycles.	Biological: ONCOS-102; ONCOS-102 will be administered intraperitoneally infusion at weekly intervals for 6 weeks.; Drug: Durvalumab; Durvalumab will be administered by IV infusion once every four weeks for a total of 12 four-week cycles.; Other Name: MEDI4736
Experimental: Cohort 1: Platinum-resistant epithelial ovarian cancer; ONCOS-102 will be administered for a total of 6 weeks, while durvalumab will be administered for a total of 12 cycles, starting on Day 15.	Biological: ONCOS-102; ONCOS-102 will be administered intraperitoneally infusion at weekly intervals for 6 weeks.; Drug: Durvalumab; Durvalumab will be administered by IV infusion once every four weeks for a total of 12 four-week cycles.; Other Name: MEDI4736
Experimental: Cohort 2: Colorectal cancer; ONCOS-102 will be administered for a total of 6 weeks, while durvalumab will be administered for a total of 12 cycles, starting on Day 15.	Biological: ONCOS-102; ONCOS-102 will be administered intraperitoneally infusion at weekly intervals for 6 weeks.; Drug: Durvalumab; Durvalumab will be administered by IV infusion once every four weeks for a total of 12 four-week cycles.; Other Name: MEDI4736

Outcome Measures

Primary Outcome Measures :

1. Number of Adverse Events [ Time Frame: up to 15 months ]
   Clinical laboratory tests, vital sign and weight measurements, physical exams, performance status evaluation, imaging scans and any other medically indicated assessments, including subject interviews, will be performed to detect new abnormalities and deteriorations of any pre-existing conditions. The investigator will evaluate any laboratory abnormalities for clinical significance, and clinically significant abnormalities will be recorded as adverse events. All clinically significant abnormalities and deteriorations from time of signing the informed consent to the end of study visit will be recorded in the Case Report Forms as adverse events and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

Secondary Outcome Measures :

1. Clinical Benefit (Complete Response, Partial Response and Stable Disease) for Cohorts 1 & 2 [ Time Frame: up to 24 weeks ]
   Clinical Benefit is defined as percentage of subjects who are in the study and not in progression at the end of Week 24.
2. Objective Response Rate for Cohorts 1 & 2 [ Time Frame: up to 15 months ]
3. Progression-free survival for Cohorts 1 & 2 [ Time Frame: Up to 15 months ]
4. Overall Survival for Cohorts 1 & 2 [ Time Frame: up to 4 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects with peritoneal disease who have failed prior standard chemotherapy and have histologic confirmation of epithelial ovarian cancer or metastatic colorectal cancer (CRC) including cancer originating from the appendix.
2. Subject is willing to undergo a core needle biopsy during screening and Cycle 2, Study Week 5. Archival tumor samples are requested, but are not required for eligibility.
3. Previously treated for advanced cancer with no additional therapy options available known to prolong survival.
4. Laboratory parameters for vital functions should be in the normal range or not clinically significant.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

1. Treatment with an investigational agent within 4 weeks of starting study treatment or prior treatment with a checkpoint inhibitor (cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) antibodies).
2. Subject has known active central nervous system metastasis, glioma and nervous system malignancies including carcinomatous meningitis. Subjects with asymptomatic brain metastases or spinal cord compression who have been treated, are considered stable, and who have not received corticosteroids or anticonvulsants for at least 28 days prior to screening may be included. Subject has other active malignancy.
3. Known immunodeficiency or known to have evidence of acute or chronic or human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C or other uncontrolled inter-current illnesses.
4. Ongoing bowel perforation or presence of bowel fistula or abscess or history of small or large bowel obstruction within 3 months of registration, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom-free for more than 3 months.
5. Subjects with clinically significant cardiovascular disease, history of organ transplant or allogeneic bone marrow transplant, active known or history of autoimmune disease that might recur or major surgery within 28 days prior to the first dose or still recovering from prior surgery.

Contacts and Locations

Locations

United States, California

Research Facility

San Diego, California, United States, 92093-0698

United States, Florida

Research Facility

Miami, Florida, United States, 33136

United States, New York

Research Facility

Buffalo, New York, United States, 14263

Research Facility

New York, New York, United States, 10065

United States, Ohio

Research Facility

Toledo, Ohio, United States, 43614

United States, Virginia

Research Facility

Charlottesville, Virginia, United States, 22903

Sponsors and Collaborators

Ludwig Institute for Cancer Research

Cancer Research Institute, New York City

MedImmune LLC

Targovax ASA

More Information

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT02963831
• Other Study ID Numbers: LUD2015-008
• First Posted: November 15, 2016
• Last Update Posted: November 16, 2021
• Last Verified: November 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ludwig Institute for Cancer Research:

Oncos-102; Durvalumab; Peritoneal; Cyclophosphamide

Additional relevant MeSH terms:

Appendiceal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Cecal Neoplasms; Cecal Diseases; Durvalumab; Antineoplastic Agents, Immunological; Antineoplastic Agents